Heart disease is the leading cause of death and disability in both industrialized nations and the developing world, accounting for approximately 40% of all human mortality. Many patients who survive develop a chronic form of heart disease called congestive heart failure (CHF), which is associated with a progressive deterioration of the heart muscle, scar formation, LV (Left Ventricular) dilation and dysfunction. Patients with severe ischemic heart failure have a high morbidity and mortality, being heart transplant the only available definitive therapy.
Recently, different source of stem cells have been tested in human patients that underwent a MI (Myocardial Infarction), including adult peripheral blood stem cells (APBSCs) and bone marrow-derived stem cells (BMDSCs) (Losordo, D. W., et al., Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina: a phase I/IIa double-blind, randomized controlled trial. Circulation, 2007. 115(25): p. 3165-72; Schachinger, V., et al., Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med, 2006. 355(12): p. 1210-21). Improvement in the LV ejection fraction has been reported in the majority of the trials (Schachinger, V., et al., Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med, 2006. 355(12): p. 1210-21; Passier, R., L. W. van Laake, and C. L. Mummery, Stem-cell-based therapy and lessons from the heart. Nature, 2008. 453(7193): p. 322-9); however, the functional improvement is still modest (ejection fraction below 5%). Therefore, there is a need for alternative approaches to (i) increase the therapeutic effect of stem cells and to (ii) treat old patients that have adult stem cells with impaired biological activity (e.g. diabetic patients, etc. . . . ) (Passier, R., L. W. van Laake, and C. L. Mummery, Stem-cell-based therapy and lessons from the heart. Nature, 2008. 453(7193): p. 322-9).
CD34+ cells isolated from human cord blood may be a promising cellular therapy for heart regeneration. These stem cells can be used autologously, can differentiate into vascular cells either in vitro or in vivo (Le Ricousse-Roussanne, S., et al., Ex vivo differentiated endothelial and smooth muscle cells from human cord blood progenitors home to the angiogenic tumor vasculature. Cardiovasc Res, 2004. 62(1): p. 176-84) and augment the neovascularization in animal models of myocardial ischemia (Ma, N., et al., Human cord blood cells induce angiogenesis following myocardial infarction in NOD/SCID-mice. Cardiovasc Res, 2005. 66(1): p. 45-54; Hirata, Y., et al., Human umbilical cord blood cells improve cardiac function after myocardial infarction. Biochem Biophys Res Commun, 2005. 327(2): p. 609-14) CD34+ cells isolated from human cord blood have several advantages as compared to APBSCs and BMDSCs, including higher proliferation rate, relatively low risk of giving unwanted cells in vivo (in opposition to the risks described for BMDSCs), and a suitable cell therapy for patients that underwent a MI and have human peripheral blood CD34+ cells with impaired function [5, 10]. For clinical efficacy, it is imperative that stem cells or their progenies survive and engraft into the host tissue. Unfortunately, many cells die a few days after delivery (Ma, N., et al., Human cord blood cells induce angiogenesis following myocardial infarction in NOD/scidSCID-mice. Cardiovasc Res, 2005. 66(1): p. 45-54; Hirata, Y., et al., Human umbilical cord blood cells improve cardiac function after myocardial infarction. Biochem Biophys Res Commun, 2005. 327(2): p. 609-14; Henning, R. J., et al., Human umbilical cord blood progenitor cells are attracted to infarcted myocardium and significantly reduce myocardial infarction size. Cell Transplant, 2006. 15(7): p. 647-58).